Lathosterol and other noncholesterol sterols during treatment of hypercholesterolemia with lovastatin alone and with cholestyramine or guar gum.

Abstract

Sixty-two patients aged 19-64 years with primary hypercholesterolemia (mean level of total cholesterol, 10.8 mmol/l) were treated with 80 mg/day lovastatin (L) alone for 18 weeks and, after randomization to either L + 20 g/day guar gum (L + GG) or L + 16 g/day cholestyramine (L + C) treatments, for an additional 18 weeks. The total cholesterol level declined from baseline by 34% during L and by 44% and 48% during L + GG and L + C, respectively. In terms of micromoles per millimole of cholesterol, serum levels of the cholesterol synthesis precursors cholestenol, desmosterol, and lathosterol were decreased and those of the plant sterols campesterol and sitosterol were increased by treatment with L. The serum contents of cholesterol precursors were increased markedly after the combination of either GG or C with L, but the increase was greater after the addition of C (e.g., the lathosterol to cholesterol ratio was 51% versus 212% for L + GG and L + C, respectively; p less than 0.001). Thus, a higher rate of removal of bile acids by C than by GG reduced more effectively the low density lipoprotein cholesterol level but simultaneously stimulated cholesterol synthesis compensatorily to a higher level even under concurrent treatment with L. The serum sitosterol to cholesterol ratio declined by 13% during L + GG but increased by 49% during L + C compared with the value under L alone, suggesting different effects of GG and C on the metabolism of plant sterols.